A Novel Method of Coupling In Situ Time-Resolved FTIR and Microwave Irradiation: Application to the Monitoring of...

Traditional synthetic methods, often limited by inefficiency, are increasingly being replaced by sustainable alternatives. This study presents a green approach combining microwave irradiation with in situ FTIR spectroscopy for real-time monitoring and optimising nitrogen-heterocycle synthesis, focusing on quinoxalines. Although both microwave-assisted synthesis and time-resolved FTIR are established techniques, their combined application remains underexplored, limiting their synergistic potential. The methodology was applied to synthesising 2,3-diphenylquinoxaline, a compound of interest in medicinal chemistry. Optimisation of the condensation between benzil and 1,2-phenylenediamine was achieved by exploiting the accelerated kinetics of microwave irradiation and continuous monitoring via in situ FTIR. Three catalytic systems were evaluated-hydrochloric acid (Brønsted acid), Montmorillonite K10 (heterogeneous catalyst), and molecular iodine (halogen/Lewis acid)-alongside a range of solvents, including ethanol, methanol, water, acetonitrile, ethyl acetate, dimethyl sulfoxide, and dichloromethane. Iodine proved to be the most efficient catalyst, while acetonitrile and ethyl acetate provided the most effective solvent systems. This integrated monitoring strategy reduces reliance on trial-and-error optimisation and establishes a streamlined, scalable, and efficient protocol. The dual-technique approach highlights a versatile pathway for advancing green synthetic methodologies with applications across the chemical and pharmaceutical industries.